1yns Citations

Crystal structure of human E1 enzyme and its complex with a substrate analog reveals the mechanism of its phosphatase/enolase activity.

J. Mol. Biol. 348 917-26 (2005)
Cited: 16 times
EuropePMC logo PMID: 15843022


Enolase-phosphatase E1 (MASA) is a bifunctional enzyme in the ubiquitous methionine salvage pathway that catalyzes the continuous reactions of 2,3-diketo-5-methylthio-1-phosphopentane to yield the aci-reductone metabolite using Mg2+ as cofactor. In this study, we have determined the crystal structure of MASA and its complex with a substrate analog to 1.7A resolution by multi-wavelength anomalous diffraction and molecular replacement techniques, respectively. The structures support the proposed mechanism of phosphatase activity and further suggest the probable mechanism of enolization. We establish a model for substrate binding to describe in detail the enzymatic reaction and the formation of the transition state, which will provide insight into the reaction mechanisms of other enzymes in the same family.

Articles - 1yns mentioned but not cited (1)

  1. Crystal structure of ED-Eya2: insight into dual roles as a protein tyrosine phosphatase and a transcription factor. Jung SK, Jeong DG, Chung SJ, Kim JH, Park BC, Tonks NK, Ryu SE, Kim SJ. FASEB J. 24 560-569 (2010)

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Articles citing this publication (14)

  1. Protein biomarkers in a mouse model of extremes in trait anxiety. Ditzen C, Jastorff AM, Kessler MS, Bunck M, Teplytska L, Erhardt A, Krömer SA, Varadarajulu J, Targosz BS, Sayan-Ayata EF, Holsboer F, Landgraf R, Turck CW. Mol. Cell Proteomics 5 1914-1920 (2006)
  2. 2-Keto-4-methylthiobutyrate, an intermediate in the methionine salvage pathway, is a good substrate for CtBP1. Achouri Y, Noël G, Van Schaftingen E. Biochem. Biophys. Res. Commun. 352 903-906 (2007)
  3. Mechanistic diversity in the RuBisCO superfamily: a novel isomerization reaction catalyzed by the RuBisCO-like protein from Rhodospirillum rubrum. Imker HJ, Singh J, Warlick BP, Tabita FR, Gerlt JA. Biochemistry 47 11171-11173 (2008)
  4. Functional identification of APIP as human mtnB, a key enzyme in the methionine salvage pathway. Mary C, Duek P, Salleron L, Tienz P, Bumann D, Bairoch A, Lane L. PLoS ONE 7 e52877 (2012)
  5. Phosphoproteome analysis during larval development and metamorphosis in the spionid polychaete Pseudopolydora vexillosa. Chandramouli KH, Mok FS, Wang H, Qian PY. BMC Dev. Biol. 11 31 (2011)
  6. Differential expression of proteins and phosphoproteins during larval metamorphosis of the polychaete Capitella sp. I. Chandramouli KH, Soo L, Qian PY. Proteome Sci 9 51 (2011)
  7. Expanding the spectrum of microdeletion 4q21 syndrome: a partial phenotype with incomplete deletion of the minimal critical region and a new association with cleft palate and Pierre Robin sequence. Bhoj E, Halbach S, McDonald-McGinn D, Tan C, Lande R, Waggoner D, Zackai E. Am. J. Med. Genet. A 161A 2327-2333 (2013)
  8. Defence gene expression profiling to Ascochyta rabiei aggressiveness in chickpea. Leo AE, Linde CC, Ford R. Theor. Appl. Genet. 129 1333-1345 (2016)
  9. MtnBD is a multifunctional fusion enzyme in the methionine salvage pathway of Tetrahymena thermophila. Nakano T, Ohki I, Yokota A, Ashida H. PLoS ONE 8 e67385 (2013)
  10. Crystal structure of MtnX phosphatase from Bacillus subtilis at 2.0 angstroms resolution provides a structural basis for bipartite phosphomonoester hydrolysis of 2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate. Xu Q, Saikatendu KS, Krishna SS, McMullan D, Abdubek P, Agarwalla S, Ambing E, Astakhova T, Axelrod HL, Carlton D, Chiu HJ, Clayton T, DiDonato M, Duan L, Elsliger MA, Feuerhelm J, Grzechnik SK, Hale J, Hampton E, Han GW, Haugen J, Jaroszewski L, Jin KK, Klock HE, Knuth MW, Koesema E, Miller MD, Morse AT, Nigoghossian E, Okach L, Oommachen S, Paulsen J, Reyes R, Rife CL, Schwarzenbacher R, van den Bedem H, White A, Wolf G, Hodgson KO, Wooley J, Deacon AM, Godzik A, Lesley SA, Wilson IA. Proteins 69 433-439 (2007)
  11. Integration of metabolomics and expression of enolase-phosphatase 1 links to hepatocellular carcinoma progression. Zhuang H, Qiang Z, Shao X, Wang H, Dang Y, Wang Z, Wu F, Wei W, Li Y. Theranostics 9 3639-3652 (2019)
  12. Mutagenesis of the enolase-phosphatase gene in Xanthomonas oryzae pv. oryzae affects growth on methylthioadenosine and in vivo S-adenosylmethionine pools. Zhang Y, Zhang G, Zhang J, Wang X, Wang J. Arch. Microbiol. 191 773-783 (2009)
  13. Proteome of the rete testis fluid from tropically-adapted Morada Nova rams. van Tilburg MF, Sousa SD, Ferreira de Melo RB, Moreno FB, Monteiro-Moreira AC, Moreira RA, de Alencar Moura A. Anim. Reprod. Sci. 176 20-31 (2017)
  14. Revisiting the methionine salvage pathway and its paralogues. Sekowska A, Ashida H, Danchin A. Microb Biotechnol 12 77-97 (2019)